Degeneration of heart valves with congenital malformations, such as bicuspid aortic valve (BAV) and associated pathology of the aortic apparatus (including the root, sinus, and the valve leaflets), is a common clinical problem resulting in significant patient management issues. The normal trileaflet aortic valve (TAV) functional dynamics involves complex interaction between the valve complex including the aortic root, sinuses of Valsalva, the ascending aorta, and the valve leaflets interacting with the flowing blood. The AV leaflets are multi-layered structures exhibiting non-linear mechanical properties undergoing complex deformation during the opening and closing phases. The relationship between the stresses developed on the leaflets and the aortic valve apparatus during the cardiac cycle and the valvular pathology such as leaflet calcification and valvular incompetence are poorly understood. These can be related to the modified valve geometry and blood flow dynamics due to the altered valve geometry and tissue properties. During the first four and half years of the project (Aug. 03 - Feb. 08), we have concentrated on the development of a robust, fluid-structure interaction (FSI) algorithm. The algorithm developed include: 2D and 3D FSI simulation of mechanical valve closure dynamics including the incorporation of particle dynamics to compute the stresses that the platelets in the flowing blood are subjected to in the vicinity of the valve structures that can lead to thrombus formation;quasi-static and dynamic finite element (FE) analysis of native and bioprosthetic heart valves during a cardiac cycle incorporating the non-linear anisotropic material properties, and the merging of the FE and computational fluid dynamics code to develop a robust, rigorously validated FSI code for the dynamic simulation of native and bioprosthetic aortic valves. In this revised competing renewal application, we propose to apply our experimental and simulation capabilities to: 1) Perform detailed analysis of the native TAV dynamics;and 2) Identify the alterations (both fluid and structural) dynamics due to congenital malformations such as the BAV. The long-term goals of this project are to develop a detailed multi-scale simulation of normal and congenital aortic valve in order to provide an objective basis for the treatment modalities for aortic valvular diseases. The proposed work will result in an improved understanding of the impact of mechanical properties, geometry, and coupled fluid- solid mechanics on the native valve pathology. The results will also provide a basis for the development of novel repair strategies and for engineered valve substitutes.